Development and implementation of a cell-based assay to discover agonists of the nuclear receptor REV-ERBα
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Development and implementation of a cell-based assay to discover agonists of the nuclear receptor REV-ERBα. / Hering, Yuliya; Berthier, Alexandre; Duez, Helene; Lefebvre, Philippe; Deprez, Benoit; Gribbon, Philip; Wolf, Markus; Reinshagen, Jeanette; Halley, Francoise; Hannemann, Juliane; Böger, Rainer; Staels, Bart; Gul, Sheraz.
In: Journal of biological methods, Vol. 5, No. 3, 2018, p. e94.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Development and implementation of a cell-based assay to discover agonists of the nuclear receptor REV-ERBα
AU - Hering, Yuliya
AU - Berthier, Alexandre
AU - Duez, Helene
AU - Lefebvre, Philippe
AU - Deprez, Benoit
AU - Gribbon, Philip
AU - Wolf, Markus
AU - Reinshagen, Jeanette
AU - Halley, Francoise
AU - Hannemann, Juliane
AU - Böger, Rainer
AU - Staels, Bart
AU - Gul, Sheraz
PY - 2018
Y1 - 2018
N2 - The nuclear receptors are transcription factors involved in the regulation of a variety of physiological processes whose activity can be modulated by binding to relevant small molecule ligands. Their dysfunction has been shown to play a role in disease states such as diabetes, cancer, inflammatory diseases, and hormonal resistance ailments, which makes them interesting targets for drug discovery. The nuclear receptor REV-ERBα is involved in regulating the circadian rhythm and metabolism. Its natural ligand is heme and there is significant interest in identifying novel synthetic modulators to serve as tools to characterize its function and to serve as drugs in treating metabolic disorders. To do so, we established a mammalian cell-based two-hybrid assay system capable of measuring the interaction between REV-ERBα and its co-repressor, nuclear co-repressor 1. This assay was validated to industry standard criteria and was used to screen a subset of the LOPAC®1280 library and 29568 compounds from a diverse compound library. Profiling of the primary hits in a panel of counter and selectivity assays confirmed that REV-ERBα activity can be modulated pharmacologically and chemical scaffolds have been identified for optimization.
AB - The nuclear receptors are transcription factors involved in the regulation of a variety of physiological processes whose activity can be modulated by binding to relevant small molecule ligands. Their dysfunction has been shown to play a role in disease states such as diabetes, cancer, inflammatory diseases, and hormonal resistance ailments, which makes them interesting targets for drug discovery. The nuclear receptor REV-ERBα is involved in regulating the circadian rhythm and metabolism. Its natural ligand is heme and there is significant interest in identifying novel synthetic modulators to serve as tools to characterize its function and to serve as drugs in treating metabolic disorders. To do so, we established a mammalian cell-based two-hybrid assay system capable of measuring the interaction between REV-ERBα and its co-repressor, nuclear co-repressor 1. This assay was validated to industry standard criteria and was used to screen a subset of the LOPAC®1280 library and 29568 compounds from a diverse compound library. Profiling of the primary hits in a panel of counter and selectivity assays confirmed that REV-ERBα activity can be modulated pharmacologically and chemical scaffolds have been identified for optimization.
U2 - 10.14440/jbm.2018.244
DO - 10.14440/jbm.2018.244
M3 - SCORING: Journal article
C2 - 31453244
VL - 5
SP - e94
JO - Journal of biological methods
JF - Journal of biological methods
SN - 2326-9901
IS - 3
ER -
